Progress in the Science of Cannabis Consumables

Concerns over stability and bioavailability continue to challenge the consumables landscape, although research efforts are yielding interesting and important insights

Cannabis consumables have grown in popularity by leaps and bounds. This includes a move away from traditional consumables — such as smoking and vaping products — closer towards edibles, beverages, sublingual drops, and other modes of consumption.  Whether due to proliferation and availability of a wider range of products, or the result of perceived health hazards associated with smoking and vaping, the trend will likely continue for the foreseeable future — for both medicinal and recreational use.

It has long been known that the most straightforward route for bioavailability is through inhalation. Oral consumption, on the other hand, is known to be fraught with challenges such as suboptimal absorption, dosing inaccuracies, and variations in time and duration of delivery. These challenges are likely due to the chemical nature of the cannabis compounds and the consumable “vehicles” with which they travel into the body.

Having both water soluble and insoluble qualities (aliphatic), cannabis compounds can attach to lipids (fats) and other compounds in consumables, making them less available for absorption in the GI tract. Depending on the type of consumable, cannabis compounds may exhibit limited solubility or loss of solubility over time. In certain formulations, such as infused drinks, this may be a reason for the observed inaccuracies in dosage labelling or concerns over shelf life.

Whether brownies or chocolates, medicinal or otherwise, the concerns over stability and bioavailability are serious and continue to challenge the consumables landscape. Fortunately, research efforts are underway and ongoing — yielding important insight on the science of cannabis consumables.

Before we dive into the latest published results, we should define some terminology — if only for review.

What is Solubility?

Simply stated, solubility is the likelihood that a compound or chemical will dissolve in water and remain as a solution. Water is polar and has both positive and negative charge. Compounds which also have charge can interact with water molecules and remain “solvated” or soluble.  Insoluble compounds lack sufficient charge and will not dissolve or be stable in aqueous or water-like solutions. There are varying degrees of solubility and insolubility which dictate compound behavior. Solubility of cannabinoids (such as THC and CBD) depend on the chemical nature of the solvent, and can be influenced by pH, salt, heat, pressure, and chemical additives in the formulations.

What is Stability?

In chemistry, stability is the likelihood that a compound will remain in its current chemical state. This is opposed to reactivity, which is the potential for a compound to react with another substance and alter its chemical state. A compound that is stable in solution has a low likelihood of changing and becoming unstable or undergoing degradation. Substances in solution, such as surfactants, may help stabilize the compound while other factors, heat, light, pH, may serve to destabilize the compound.

What is Bioavailability?

Bioavailability is the extent to which a compound or drug is available to its intended biological target. A formulation that exhibits high bioavailability is well-suited to enter the body through whatever route is chosen, inhalation, digestion, etc.  In the process, the drug or compound remains stable and is available to elicit the intended biological effects. Low bioavailability means the compound does not reach its target, as a possible result of reactivity, degradation, and/or malabsorption.

What is Emulsification?

In medicine, it is the process of mixing two liquids or solutions that are typically unmixable. Through the use of chemical surfactants and the application of mechanical or vibrational force, a mixture or emulsion can be formed. There are three classes of emulsion: common, microemulsions, nanoemulsions.

What is Sonication?

The use of sound waves to agitate and disperse particles in solution is termed sonication. This is typically achieved by converting electrical signal to vibrational energy. A common application of sonication is to induce dissolution of particles or compounds into a liquid or solvent.

What is Microfluidics?

Microfluidics is the science of manipulating fluids — their behavior, flow characteristics, viscosity, and other parameters — by constraining the fluids to micro-scale volumetric spaces and exerting physical force through flow rate.

These latter few definitions may seem independent, but they can also be closely related — as shown in a recent research investigation.

The Latest Cannabis Consumables Research

Recently published in the journal Nature and titled “Comparing microfluidics and ultrasonication as formulation methods for developing hempseed oil nanoemulsions for oral delivery applications”, the authors of this paper compared the performance of sonication and microfluidic methods in preparation hempseed nanoemulsions. The resulting formulations were subsequently analyzed to determine compound encapsulation efficiency and average droplet size. Additional tests were performed to assess the delivery and functionality of the prepared formulations in bioavailability experiments.

Without venturing too far into the weeds (we’ll save that for you), here is a synopsis of the conclusions:

• Hempseed nanoemulsions were successfully formulated using an optimized sonication method.
• The use of an emulsifier (lecithin) favored nanoemulsion formation, which affected the entrapment efficiency, particle size, and other physical qualities of the droplets.
• This formulation displayed release behavior in GI tract simulatations and cell-based tests, demonstrating productive transportation of particles and bioavailability in vitro.
• Nanoemulsions formed by microfluidic methods contained on average smaller particles compared with sonication, with increased stability at room temperature.
• The size and stability of the particle droplets could be modified by adjusting the organic:aqueous ratio and microfluidic flow rate.
• Both techniques result in nanoemulsions that exhibit good transportation and bioavailability characteristics.

Although much work has been done up until the point on the chemical formulation of emulsions, limited research has focused on the comparison of high-energy methods — sonication and microfluidics — on cannabis nanoemulsion stability and bioactivity.

Instruments and Solutions for Consumables Research

The work described used analytical methods to examine the physical and biological qualities of the formulations. To accomplish these detailed and challenging experiments, the investigators used the following approaches:

• Nutritional analysis and fatty acid profile of hempseed oil were measured by GC/MS using a PerkinElmer Clarus 680-GC-SQ8T mass spectrometer.
• Confirmation of the polyunsaturated and saturated fatty acid content of hempseed oil was measured by NMR using a Bruker Avance Cryoprobe 600 MHz spectrometer.
• Cannabinoid content was deduced by LC/MS using an Agilent 1290 Infinity/6530 Accurate Mass Q-TOF system with Eclipse Plus column (C18, 2.1x50 mm, 1.8 µm pore size).
• Sonicated nanoemulsions were prepared using a 1200 W Polytron PCU-2-110 high speed homogenizer and ultra-sonicator.
• A NanoAssemblr Benchtop instrument was used for microfluidic formulations.
• Emulsion droplet diameters were determined by dynamic light scattering (DLS) using a Litesizer 500 DLS system from Anton Paar.

Multiple biochemical and cell biological reagents and equipment were used for bioavailability experiments.

Outlook

The depth and rigor of this study are indicative of the state of cannabis science and how approaches used in drug delivery research may be directly applied to facilitate cannabis delivery.

The combination of analytical instruments and methods used in the work exemplifies the importance of instrument providers in pushing cannabis consumables science forward.

Studies such as this are foretelling for the consumables field — we can’t wait to see the types of research and products that continue to grow from this interesting and important area of cannabis science.

Visit the LabX Cannabis Laboratory application page for further resources and product listings

Updated Nov 2022